الفهرس 
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Abstract
Egypt has one of the highest prevalence rates of hepatitis C virus (HCV) infection in the world. The HCV epidemic appears to have been initiated by vigorous public-health campaigns using intravenous tartar emetic from the 1950s until 1982 to eradicate schistosomiasis. This iatrogenic mode of infection has resulted in a high incidence of hepatic morbidity and mortality from the late complications of HCV infection, such as chronic hepatitis, cirrhosis and hepatocellular carcinoma. Among the six major HCV genotypes found worldwide, genotype 4 is the most predominant in Egypt with 4a as the dominant subtype.
The goal of therapy is to eradicate HCV infection in order to prevent the complications of HCV-related liver disease. Till 2011,when we planned our study, the standard of care(SOC) of HCV was by the combination of PEG-IFN and Ribavirin (RBV),that consisted of weekly subcutaneous injection of 180μg of PEG- IFN and a daily oral RBV tablets, according to the weight, 1000-1200 mg/day (cut off at 75kg).
It was found that the treatment of HCV using combination of pegylated interferon (PEG-IFN) plus ribavirin fails in about 50% of the patients and is physically and economically demanding. Thus, it is highly important to understand the mechanisms of non-response to overcome it and to identify factors that can help to predict the chance of each patient to respond to the treatment. Different elements are associated with nonresponse: (i) viral factors, (ii) host factors and (iii) molecular mechanisms induced by HCV proteins to inhibit the IFN signaling pathway.
Differences in host genetics are believed to influence the outcome of hepatitis C virus (HCV) infection. The interleukin28B (IL28B) variability has a strong impact on viral clearance, either spontaneously or drug- induced, in HCV infected patients
The aim of the our study was to assess the effect of IL28B polymorphism (rs12979860) and other studied parameters on the response to the pegylated-interferon (Peg-IFN)/Ribavirin treatment in the Egyptian hepatitis C virus.
One hundred subjects were included in the study, divided into four groups; group I:30 chronic HCV cases without cirrhosis, group II: 30 cirrhotic HCV cases, group III : 30 hapatocellular carcinoma (HCC) HCV +ve cases and group IV : 10 healthy controls.
In our study, the IL28 B genotype CT was the most frequent in the whole studied population and it was found in about half of the studied patients (56.67%, 56.67%, 50% of chronic HCV, cirrhotics, HCC patients respectively), followed by CC (23.33%, 30%, 36.67% of chronic HCV, cirrhotics, HCC patients respectively) then TT (20%, 13.33%, 3,33% of chronic HCV, cirrhotics, HCC patients respectively).
We did not find a significant association between the three genotypes of IL28 B in patients and disease condition.
Meanwhile, HCV RNA level(viral load) in cirrhotic patients(1.3969 x 106 ±1.48390 x 106) was significantly higher than chronic HCV non cirrhotic patients (884692 ± 1,04141 x 106 )and significantly lower than HCC patients (2.6314x106 ± 1.96024 x 106 ).
group I and II were further subdivided into two subgroups according to the response to the dual therapy pegylated=interferon(Peg-IFN)/Ribavirin at 12 and 24 weeks after the completion of HCV therapy; A: Responders with undetectable HCV RNA in serum 12 weeks (SVR 12), 24 weeks(SVR 24)after the completion of HCV therapy. B: Non-Responders including those who had detectable plasma HCV RNA at week 12/24.
In the current study, SVR12 showed significant association with non-cirrhotic patients (p = 0.001), SVR 24 showed higher association but not significant (P= 0.071) with non-cirrhotic group denoting higher response among the same group.
In the current study, higher base line INR, PT are associated with unfavorable outcomes after 3 months (SVR12) in cirrhotic group, while there is no significant predictor of SVR12 in non-cirrhotic group.
Meanwhile; direct bilirubin (P=0.017), INR(P=0.001), PT(P=0.001), prothrombin activity (P=0.004) and AFP (P=0.003) were statistically significant predictors of SVR 24 in cirrhotic patients, while there is no significant predictor of SVR 24 in non-cirrhotic group.
Although, CC patients are more prone than patients with the T allele to achieve an SVR12 in cirrhotic patients, this is not the case in HCV non cirrhotic patients, where CT/TT alleles are more prone to achieve SVR12, but this was statistically non-significant.
Concerning rates of SVR24 in our study, cirrhotic patients (genotype CC) did achieve it more frequently (7/12)as compared to genotype CT/TT (5/12), which was statistically significant (p = 0.0228), while in the non-cirrhotic group, this different genotype distribution was statistically non-significant.